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Overcoming Chemotherapy Resistance In Refractory Multiple Myeloma With Simvastatin and Zoledronic Acid

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01772719
Recruitment Status : Terminated (Principal Investigator left institution-study not continued)
First Posted : January 21, 2013
Results First Posted : November 18, 2019
Last Update Posted : November 18, 2019
James Graham Brown Cancer Center
Information provided by (Responsible Party):
University of Louisville

Brief Summary:
The purpose of this study is to examine the effect of simvastatin and zoledronic acid on M-protein and/or free light chains when added to conventional chemotherapy for the treatment of multiple myeloma patients.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Simvastatin and zoledronic acid Not Applicable

Detailed Description:
We hypothesize that the addition of simvastatin and zoledronic acid to bortezomib, thalidomide, melphalan or dexamethasone based regimens will decrease drug resistance when treating refractory multiple myeloma. We hypothesize that the addition of simvastatin and zoledronic acid will not increase the chemotherapy toxicity significantly and will be tolerable for patients. We believe simvastatin and zoledronic acid have antitumor properties and will contribute to reversal of resistance. Treatment will be significantly enhanced when these agents are combined

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Overcoming Chemotherapy Resistance In Refractory Multiple Myeloma With Simvastatin and Zoledronic Acid
Study Start Date : August 2012
Actual Primary Completion Date : November 2016
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Study Arm
Study Arm
Drug: Simvastatin and zoledronic acid
  1. Simvastatin 80 mg PO daily starting two days before starting chemotherapy and stopping two days after chemotherapy.
  2. Zoledronic acid 4 mg IV over 15 minutes on day 1 and then monthly.
Other Name: Zocor

Primary Outcome Measures :
  1. Change in Paraprotein Level and Free Light Chain (FLC) Ratio From Baseline Measurement [ Time Frame: 4 weeks after treatment begins ]
    The effect of simvastatin and zolendronic acid on M-Protein and FLC ratio will be measured 4 weeks after treatment begins, then every 4 weeks until progression of disease.

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: At start of year 2 of follow-up on all surviving participants ]
    OS(Overall survival) is measured from date of study enrollment until death.

  2. Duration of Response [ Time Frame: Year 1 follow up visits occur monthly ]
    Response will be accessed by one of the study investigators at each monthly follow up visit during year one.

  3. Progression Free Survival (PFS) [ Time Frame: At start of year 2 follow up on all surviving participants ]
    Study will estimate PFS when there is one year of follow up data for all surviving participants

  4. Duration of Response [ Time Frame: Year 2 follow up visit occur every three months ]
    Response will be assessed by one of the study investigators at each three month follow up visit for Year 2

  5. Duration of Response [ Time Frame: Year 3-5 follow up visit occurs every six months ]
    Response will be assessed by one of the study investigators at each six month follow up visit for Year 3-5

  6. Incidence Rate of Toxicity [ Time Frame: Every 12 months up to one month after treatment completion ]
    Descriptive statistics will be provided regarding incidence rates of toxicity. Patients will be monitored for safety throughout the study.

  7. Comparison of Quality of Life Scores [ Time Frame: Up to 2 months after last treatment has been completed ]
    The QOL scores taken at the start of the study and every 4 months after treatment starts will be analyzed using Wilcoxon test for paired differences

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. have a definitive diagnosis of Multiple Myeloma (using the International Myeloma Working Group Guidelines).
  2. meet one of the following two requirements:

    • Have achieved minimal response (MR) or stable disease (SD) in current treatment regimen after a minimum of two cycles.
    • Have partial response but show no further improvement in paraprotein levels in the latest two measurements.
  3. must have measurable active or symptomatic disease. Measurable disease may be paraprotein or free light chains in serum or urine, or the presence of bone marrow plasma cells, defined by one or more of the following criteria:

    • Presence of serum M-protein concentration > 1g/dL.
    • Urine M-protein excretion > 200mg in 24-hour urine collection.
    • Serum free light chain concentration ≥ 10mg/dL and abnormal kappa/lambda ratio.
    • Urine free light chain concentration ≥ 100mg/L and abnormal kappa/lambda ratio.
    • Bone marrow plasma cell percentage ≥ 30% (if no detectable M-protein or FLC.)
  4. Age > 18 years of age.
  5. If female with reproductive capacity: on effective means of birth control during the entire duration of the treatment.
  6. Patients must have recovered from acute toxicities resulting from therapy administered prior to entering this study to grade 1 or less (CTCAE 4) Alopecia may not be resolved.
  7. Ability to understand and willingness to sign a written informed consent document.
  8. Life expectancy of greater than 8 weeks.
  9. ECOG performance status 0, 1, or 2 (Karnofsky > 60%; see Appendix A).
  10. have adequate bone marrow function as defined below:

    • absolute neutrophil count > 500/ul
    • platelets > 30,000/ul
  11. have adequate liver function as defined below:

    • total bilirubin < 2 times the upper limit of normal
    • AST(SGOT), ALT(SGPT) < 3 x upper limit of normal
  12. have adequate renal function as defined by a creatinine clearance > 40 mL/min (measured or estimated by the Cockcroft-Gault formula).
  13. have no signs of significant rhabdomyolysis determined by CPK levels with a CK < 5 times the upper limit of normal.

Exclusion Criteria:

  1. have not received any chemotherapy treatment for multiple myeloma prior to being enrolled in the study.
  2. show progressive disease or are not tolerating current chemotherapy regimen.
  3. were receiving simvastatin (dose > 40mg/day) while receiving current chemotherapy regimen for multiple myeloma.
  4. failed or progressed on more than two chemotherapy regimens, including current treatment; prior to enrolling in this study.
  5. receiving any other investigational agent(s).
  6. Active second malignancy in the last 5 years except for non-melanoma skin cancer or carcinoma-in-situ.
  7. Pregnant women are ineligible, as treatment involves unforeseeable risks to the embryo or fetus. Female patients with reproductive capacity are required to use effective means of birth control during the entire duration of the treatment.
  8. History of hypersensitivity reactions attributed to simvastatin or zoledronic acid.
  9. receiving medications that may increase risk of rhabdomyolysis such as itraconazole, ketoconazole, erythromycin, cyclosporine, amiodarone, verapamil, clarithromycin, nefazodone, ranolazine, HIV protease inhibitors, gemfibrozil, posaconazole, danazol, amiodarone, diltiazem and amlodipine.
  10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myopathy, untreated hypothyroidism, hereditary myopathy in the family history, unstable angina pectoris, liver disease not due to multiple myeloma, cardiac arrhythmia that is symptomatic or not rate controlled, active connective tissue disease, active autoimmune disease, or psychiatric illness/social situations that would limit compliance with study requirements.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01772719

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United States, Kentucky
James Graham Brown Cancer Center
Louisville, Kentucky, United States, 40202
Sponsors and Collaborators
University of Louisville
James Graham Brown Cancer Center
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Principal Investigator: Cesar Rodriguez, MD Dept. of Med Admin.

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Responsible Party: University of Louisville Identifier: NCT01772719    
Other Study ID Numbers: BCC-HEM-11-003
First Posted: January 21, 2013    Key Record Dates
Results First Posted: November 18, 2019
Last Update Posted: November 18, 2019
Last Verified: October 2019
Keywords provided by University of Louisville:
refractory multiple myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Zoledronic Acid
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Bone Density Conservation Agents
Physiological Effects of Drugs